The long term objectives of this application are to obtain a precise understanding of how genetic variants[unreadable] located in the chromosomal region containing the SLAM family of cell surface receptors major can influence[unreadable] an individual's risk to developing systemic lupus erythematosus (SLE); a chronic and debilitating[unreadable] inflammatory disease. The MHC region is a large region on chromosome 1q that contains multiple genes[unreadable] that are involved in cell-cell interactions and control of the immune response in the human immune system.[unreadable] Such an understanding will improve our knowledge of the mechanisms that lead to this and potentially other[unreadable] inflammatory diseases and may provide important molecular markers of disease. This study takes full[unreadable] advantage of the knowledge of the patterns of genetic variation in the human and mouse genomes as well[unreadable] as the relevant technological platforms (laboratory and analytical). In particular this project takes advantage[unreadable] of the preliminary SNP haplotype map of the SLAM region that we have created as well as that of the[unreadable] International HapMap project in order to select the most informative set of SNPs for the screening phase of[unreadable] the association study. This screening set of SNPs will be applied to large well-charcterized SLE patient[unreadable] cohorts. Comprehensive association mapping of the regions identified in this screen will be pursued in the[unreadable] largest collection of SLE patients and controls (family- and population-based). In addition, recent work has[unreadable] demonstrated the importance of expression of different spice forms in susceptibility to autoimmune disease,[unreadable] however very little is known about the existence and expression patterns of splice forms of most genes in the[unreadable] genome. We will therefore characterize the gene expression pattern at the level of mRNA as well as cell[unreadable] surface protein expression in immunologically relevant cells from SLE patients and control individuals.[unreadable] This work promises to have an impact on public health by identifying the genetic factors that influence an[unreadable] individual's susceptibility to systemic lupus erythematosus, a chronic inflammtory disease. This work will[unreadable] also provide important molecular markers of diseases that may be useful in clinical mangement of this[unreadable] debilitating disease.